Sirtinol abrogates late phase of cardiac ischemia preconditioning in rats

Abstract

The aim of this study was to investigate the effect of sirtinol, as an inhibitor of sirtuin NAD-dependent histone deacetylases, on myocardial ischemia reperfusion injury following early and late ischemia preconditioning (IPC). Rats underwent sustained ischemia and reperfusion (IR) alone or proceeded by early or late IPC. Sirtinol (S) was administered before IPC. Arrhythmias were evaluated based on the Lambeth model. Infarct size (IS) was measured using triphenyltetrazolium chloride staining. The transcription level of antioxidant-coding genes was assessed by real-time PCR. In early and late IPC groups, IS and the number of arrhythmia were significantly decreased (P < 0.05 and P < 0.01 vs IR, respectively). In S + early IPC, incidences of arrhythmia and IS were not different compared with the early IPC group. However, in S + late IPC the IS was different from the late IPC group (P < 0.05). In late IPC but not early IPC, transcription levels of catalase (P < 0.01) and Mn-SOD (P < 0.05) increased, although this upregulation was not significant in the S + late IPC group. Our results are consistent with the notion that different mechanisms are responsible for early and late IPC. In addition, sirtuin NAD-dependent histone deacetylases may be implicated in late IPC-induced cardioprotection.

Resveratrol suppresses interleukin‐6 expression through activation of sirtuin 1 in hypertrophied H9c2 cardiomyoblasts

“…Low to moderate expression of SIRT1 has cardiovascular protective effect against cardiac hypertrophy (Sundaresan, Pillai, & Gupta, 2011) and myocardial ischemia (Safari et al, 2017).…”

Activation of SIRT1 by Resveratrol Alleviates Pressure Overload-Induced Cardiac Hypertrophy via Suppression of TGF-β1 Signaling

“…For example, SIRT1 overexpression could relieve Ang II-induced cardiomyocyte hypertrophy and apoptosis [28]. SIRT1 also could improve cardiac functions by reducing infarct size in a mouse model of myocardial infarction [29]. Another study reported that SIRT1 activation by resveratrol (Rsv) could alleviate cardiac dysfunction via mitochondrial regulation in diabetic cardiomyopathy mice [30].…”

Sirtuin Modulators in Cellular and Animal Models of Human Diseases

“…In the same model, SIRT1 overexpression increased cardiomyocytes. Also, in the late phase of cardiac ischemia preconditioning in rats, treatment of Sirtinol significantly increased the infarct size, which made them more prone to the ischemia injury ( Safari et al, 2017 ). Splitomicin, a yeast sirtuin inhibitor, had promoted carotid artery thrombus formation in a photochemical injury mouse study.…”

“…- (Heltweg et al, 2006;Marshall et al, 2011;Portmann et al, 2013;Ceballos et al, 2021;Lu et al, (Grozinger et al, 2001;Mai et al, 2005;Ota et al, 2006;Kojima et al, 2008;Kozako et al, 2012;Fong et al, 2014;Zhou et al, 2014;Safari et al, 2017;Ma et al, 2018) -H1299 non-small lung and HeLa cervical: decreased cell proliferation (Lain et al, 2008;McCarthy et al, 2012;Dai et al, 2016;Spiegelman et al, 2018;Lee et al, 2019 or quercetin activated sirtuins (Aksoy et al, 2006;Lee, 2006;Escande et al, 2013). Because this review specifically summarizes modulators that directly bind to sirtuins, we will not explain these indirect modulators in detail.…”